A new calcium(II) complex of marbofloxacin showing much lower acute toxicity with retained antibacterial activity.

Marbofloxacin (MB) is a newly developed veterinary drug with broad-spectrum antibacterial activity. In this study, a new calcium(II)-based complex of marbofloxacin, MB-Ca, was synthesized and structurally characterized by IR, ESI-MS, UV-Vis and single crystal X-ray diffraction analysis. The characterization of this complex in solution state indicated that the coordinated MB-Ca was partly retained, along with the monomeric and dimeric forms of MB. It also showed satisfactory water solubility (1.89 mg/mL), comparing with MB (2.82 mg/mL) at 35 °C. The in vitro antibacterial activity of MB-Ca was also screened towards a series of typical pathogenic bacteria, and determined by the methods of turbidimetry and disc diffusion. The results indicated it showed comparable antibacterial activity to MB. However, it exhibited higher inhibitive ability in vitro on DNA gyrase than MB alone. Furthermore, MB-Ca showed significantly lower acute toxicity (LD50, 3186 mg/kg) than MB (LD50, 1294 mg/kg) in mice, based on the in vivo acute toxicity test. The histopathological examination on the major organs of the mice by the oral administration of MB-Ca did not show obvious organic lesions, which is similar to those treated by MB. The research results suggest that MB-Ca could be further developed into a new promising metal-based veterinary drug and a better substitute of MB, showing unabated antibacterial activity along with lower toxicity.

Increased Horizontal Transmission of Recombinant Marek's Disease Virus Due to Reticuloendotheliosis Virus Long Terminal Repeat Is the Major Competitive Advantage of the Virus Being a Prevalent Strain.

GX0101 is the first field Marek's disease virus (MDV) recombinant with an REV LTR insert isolated in China. We speculated that there was a selective advantage of GX0101 becoming the more prevalent field strain from a very low percentage of recombinant virus. In the study, dual fluorescence quantitative real-time PCR (DF-qPCR) that detects GX0101 and GX0101ΔLTR simultaneously was established based on the genomic difference of GX0101 and its LTR deletion strain GX0101ΔLTR. MDV natural transmission was simulated in specific-pathogen-free (SPF) chicks, and continuous tracking of GX0101 and GX0101ΔLTR in chicks was carried out. The results showed that GX0101 possessed high horizontal transmission capacity, which could infect SPF chicks by contact in a short time and became the predominant strain following contact infections in chicken flocks. GX0101 still had a more significant advantage of horizontal transmission than GX0101ΔLTR after continuous passage even if the initially infectious dose was significantly lower. There were 72 differentially expressed MDV genes between GX0101 and GX0101ΔLTR, with the genes and gene products mainly involved in virus replication, tegument protein, glycoprotein, nucleocapsid protein, immune evasion, tumor development and/or pathogenesis, and hypothetical protein. Sixteen genes related to virus replication and transmission were significantly up-regulated. This is the first study to illuminate that increased horizontal transmission of recombinant MDV due to REV LTR was the competitive advantage of the virus being a prevalent strain and define the differential transcription profile of viral genes between GX0101 and GX0101ΔLTR. This will be helpful for in-depth study on the molecular mechanism of increased horizontal transmission of MDV by REV LTR.